EFFECT OF DIPYRIDAMOLE ON GLOMERULAR MESANGIAL CELL ECTO-5'-NUCLEOTIDASE EXPRESSION

Although dipyridamole has been extensively studied as an anti-aggregat ing agent, its mechanism of action has not been elucidated. Cultured m esangial cells were treated with dipyridamole 1-100 mu M from 6-72 h. Ecto-5'-nucleotidase activity approximately doubled (from 115 +/- 11 t o 226 +/- 14 nmol/min/mg) after treatment with 100 mu M dipyridamole f or 72 h. This effect was concentration- and time-dependent. Cyclohexim ide, an inhibitor of protein synthesis, did not alter basal 5'-nucleot idase activity. However, it prevented stimulation by 5 mu M dipyridamo le. Adenosine availability at the receptor sites was increased by dipy ridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit ade nosine uptake into the cell. Addition of dipyridamole or NBTI to the a denosine-treated mesagial cells produced an additive increase in ecto- 5'-nucleotidase activity. Dipyridamole, through its effect on extracel lular adenosine and ecto-5'-nucleotidase, may have an influence upon r egulation of the glomerular microcirculation.